A Study to Evaluate Therapeutic Targeting of Estrogen Receptor Beta in Triple Negative Breast Cancer

Overview

About this study

The primary purpose of this study is to assess the anti-tumor activity of estradiol in patients with locally advanced or metastatic triple negative breast cancer (TNBC) that expresses estrogen receptor beta (ERβ) (>25% moderate or strong nuclear staining) and who have had prior receipt of taxane and anthracycline based chemotherapy.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Pre-Screening Inclusion Criteria:

  • Women of age ≥ 18 years old.
  • History of locally advanced or metastatic breast cancer that is ERα negative (<1% nuclear staining) and HER2 negative (see note below).
    • Note: HER2 Negative Disease per 2013 ASCO/CAP guidelines, one of the following must apply:
      • 0 or 1+ by IHC and not amplified by ISH;
      • 0 or 1+ by IHC and ISH not done;
      • 2+ by IHC and and ISH results are: <6.0 HER2 signals/cell with HER2/CEP17 ratio <2.0;
      • IHC not done and not amplified by ISH.
  • ≤2 prior chemotherapy regimens for treatment of metastatic breast cancer
    Note: Prior use of monoclonal antibodies targeting PD1, PDL1 is allowed(if administered as monotherapy it is not counted as a chemotherapy regimen).
  • ECOG Performance status 0 or 1.
  • Willing to submit a biopsy specimen from locally recurrent or metastatic site (not primary) of breast cancer for ERβ staining to Mayo Clinic Anatomic Pathology.

Pre-Registration Inclusion Criteria:

  • Presence of moderate or strong nuclear ERβ staining in >25% of cells in specimen submitted during Pre-Screening Step.

  • For patients who did not have a biopsy or lacking ERα, PR, and HER2 results from a locally advanced or metastatic site performed ≤12 months prior to Pre-Registration:Willing to undergo a standard of care biopsy of locally recurrent or metastatic breast cancer for ERα, PR, and HER2 as well as additional research cores.

  • Measurable or non-measurable disease as defined by RECIST criteria (Section 11.2) that will be assessed using imaging-based evaluations (Section 11.3). Note: The tumor lesion biopsied during the pre-registration period is not considered measurable disease or a target lesion.
  • If history of brain metastases must meet the following criteria:
    • Patients with a history of brain metastases are eligible only if they are asymptomatic and have stable disease for ≥3 months, including <28 days of prior to pre-registration;
    • Not receiving steroids for brain metastases.
  • ECOG Performance status 0 or 1.
  • ≤3 prior chemotherapy regimens for treatment of metastatic breast cancer (Note: Prior use of monoclonal antibodies targeting PD1, PDL1 is allowed).
  • Women must be postmenopausal.
    • Note: Postmenopausal status is verified by:
      • Prior bilateral surgical oophorectomy; or
      • Age ≥60 years; or
      • Age <60 years with no menses for >1 year with estradiol levels within postmenopausal range, according to institutional standard.
  • Able to swallow oral medications.
  • Willingness to stop use of strong inducers or inhibitors of CYP3A4 prior to registration.
    • Note: Use of strong inducers or inhibitors is allowed during Pre-Registration as long as patient will complete course prior to Registration.

Pre-Registration Exclusion Criteria:

  • Uncontrolled intercurrent illness including, but not limited to:
    • Ongoing or active infection;
    • Symptomatic congestive heart failure;
    • Unstable angina pectoris;
    • Uncontrolled symptomatic cardiac arrhythmia;
    • Uncontrolled hypertension (defined as blood pressure >160/90).
  • Any of the following co-morbid conditions:
    • DVT/PE ≤12 months prior to pre-registration;
      • Note: Patients who are on anticoagulant therapy for maintenance are eligible as long as the DVT and /or PE occurred >6 months prior to Pre-Registration, and there is no evidence for active thrombosis (either DVT or PE).
    • Stroke ≤ months prior to pre-registration;
    • Two or more episodes of DVT and/or PE ≤ years prior to pre-registration;
    • Abnormal uterine bleeding ≤6 months prior to pre-registration;
    • History of coagulopathy.
  • Other active second malignancy other than non-melanoma skin cancers within 3 years prior to pre-registration.
    • Note: A second malignancy is not considered active if all treatment for that malignancy is completed and the patient has been disease-free for ≥3 years prior to pre-registration.

Registration Inclusion Criteria:

  • For patents who had a biopsy taken from a metastatic site ≤12 months prior to Pre-Registration: Confirmation from local lab that tumor is ERα negative (<1% nuclear staining), and HER2 negative
  • For patients who underwent a pre-registration biopsy: Histologic confirmation from local lab that tumor is ERα negative (<1% nuclear staining), and HER2 negative (see prior note in Pre-Screening Inclusion) .
  • Laboratory values ≤14 days prior to registration:
    • Hemoglobin ≥8 g/dL;
    • Platelet Count ≥75,000/mm3;
    • Creatinine ≤1.5 x upper limit of normal ULN;
    • Total Bilirubin ≤1.5 x upper limit of normal (ULN);
    • AST/SGOT ≤2.5 x upper limit of normal (ULN)*
      • *For patients with liver metastasis: ≤5 x upper limit of normal (ULN).

Registration Exclusion Criteria:

  • None of the following therapies are allowed ≤4 days prior to registration*:
    • Chemotherapy;
    • Immunotherapy;
    • Biologic therapy;
    • Hormonal therapy;
    • Monoclonal antibodies;
    • Anti-HER2 or other "targeted" (e.g., mTOR) therapy.
    • *Note: Any adverse events derived from these therapies must be ≤Grade 2 prior to starting study therapy (exception: alopecia).

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Alvaro Moreno Aspitia, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Donald Northfelt, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Matthew Goetz, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

International patient clinical studies questions